WO1999012017A1 - Procede et dispositif d'identification de principes actifs - Google Patents

Procede et dispositif d'identification de principes actifs Download PDF

Info

Publication number
WO1999012017A1
WO1999012017A1 PCT/EP1998/005328 EP9805328W WO9912017A1 WO 1999012017 A1 WO1999012017 A1 WO 1999012017A1 EP 9805328 W EP9805328 W EP 9805328W WO 9912017 A1 WO9912017 A1 WO 9912017A1
Authority
WO
WIPO (PCT)
Prior art keywords
reactants
spectrum
time
active substances
spectra
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/EP1998/005328
Other languages
German (de)
English (en)
Inventor
David Moss
Herbert Platsch
Kathrin FÜCHSLE
Ralf Masuch
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
BASF SE
Karlsruher Institut fuer Technologie KIT
Original Assignee
BASF SE
Forschungszentrum Karlsruhe GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by BASF SE, Forschungszentrum Karlsruhe GmbH filed Critical BASF SE
Priority to EP98946404A priority Critical patent/EP1009999B1/fr
Priority to AT98946404T priority patent/ATE208896T1/de
Priority to US09/508,416 priority patent/US6429015B1/en
Priority to CA2302791A priority patent/CA2302791C/fr
Priority to JP2000508971A priority patent/JP3357350B2/ja
Priority to DK98946404T priority patent/DK1009999T3/da
Priority to DE59802164T priority patent/DE59802164D1/de
Publication of WO1999012017A1 publication Critical patent/WO1999012017A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
    • G01N21/3577—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light for analysing liquids, e.g. polluted water
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/08—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/02—Devices for withdrawing samples
    • G01N1/10—Devices for withdrawing samples in the liquid or fluent state
    • G01N1/14—Suction devices, e.g. pumps; Ejector devices
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1095—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices for supplying the samples to flow-through analysers
    • G01N35/1097—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices for supplying the samples to flow-through analysers characterised by the valves
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/14—Heterocyclic carbon compound [i.e., O, S, N, Se, Te, as only ring hetero atom]
    • Y10T436/142222—Hetero-O [e.g., ascorbic acid, etc.]
    • Y10T436/143333—Saccharide [e.g., DNA, etc.]

Definitions

  • the invention relates to a method for identifying active substances according to the first claim and a device for carrying out the method according to the ninth claim.
  • MJ Swamy, T. Heimburg and D. Marsh in “Fourier-Transfor Infrared Spectroscopic Studies on Avidin Secondary Structure and Complexation with Biotin and Biotin-Lipid Assemblies", Biophysical Journal Vol. 71 (1996) 840-847 describe work on the elucidation the structure of complexes of the protein avidin with biotin and biotin lipid by Fourier transform infrared spectroscopy (FTIR) by first taking FTIR spectra of avidin in heavy water (D : 0) and then avidin with biotin or mixed biotin lipid with buffered D ; 0 as solvent and kept for several hours at room temperature, which obviously should achieve the highest possible yield of the resulting avidin complex.
  • FTIR Fourier transform infrared spectroscopy
  • FTIR spectra were again recorded from the complex. From the spectra of the avidin and Difference spectra were formed for the spectra of the avidin complex, and since this work only deals with the structure of the avidin complexes, no time-dependent -dependent spectra recorded.
  • the FTIR spectra described reflect equilibrium states in all cases. It is not the vibration spectra of bound normal hydrogen, but the - due to the higher mass shifted - vibration spectra of bound deuterium that are recorded. As a result, a comparatively thick cuvette (50 ⁇ m) can be used.
  • a chemical compound e.g. B. a protein, which is able to form a complex at a coordination point with a certain ligand, plays no role in this work, since the fact that avidin complexed with biotin was already known.
  • the invention is based on the object of developing a method for identifying active substances which enables the detection of the formation of complexes between reactants in the smallest possible volume inexpensively and flexibly and quickly with reproducible results.
  • the process should be suitable for automation.
  • an apparatus for performing the method is to be proposed. The object is achieved by the method described in the first claim and by the device described in the ninth claim. Preferred embodiments of the method are specified in the dependent claims.
  • the active substances are identified by testing the binding ability of a reactant, for example a ligand, to at least one further reactant, for example a protein.
  • a mixture is prepared from the reactants, from which an IR or FTIR spectrum is recorded at at least two different times.
  • the ligands can be measured in aqueous solution, the conventional use of deuterated solutions, for example deuterated water or deuterated buffer, not being absolutely necessary.
  • the use of a different or additional solvent may be indicated; the use of deuterated buffers or deuterated solvents can be dispensed with.
  • the mixture can be prepared in accordance with the cited prior art. However, preference is given to using high-pressure pumps (up to approx. 400 bar) and the sample loop valves known from H? LC technology.
  • the mixture should preferably be presented in a layer thickness of 1 to 25 ⁇ m, particularly preferably 8 to 15 ⁇ m.
  • the mixture is expediently produced on the way to and / or in an IR cuvette with a corresponding optical thickness.
  • the reactants When the first IR or FTIR spectrum is recorded, the reactants must at least partially still be present in unreacted form, so that the formation of the complex can be detected by the second or by further IR or FTIR spectra. Ideally, the reaction of the reactants should not have started after the mixing. This is not possible in the case of very rapid reactions due to the mixture before and / or on the way to the IR cuvette, so that some of the reactants have already reacted with one another. In the method according to the invention, a partial reaction of the reactants does not interfere as long as sufficient reactants can still react with one another and a measurement signal can be obtained. If there is too little of the reactants in the unreacted form when the first IR or FTIR spectrum is recorded, then only spectra that no longer have sufficient differences can be recorded. In such a case, the difference spectra show a zero line.
  • a first FTIR spectrum is preferably recorded immediately after the preparation of the mixture (time t ; ). "Immediately” means that the spectrum is recorded as quickly as technically possible. Since the reaction rate is the highest immediately after the reactants are brought into contact with one another, it is essential for the speed and accuracy of the process if the Recording the first spectrum, the reaction rate is still sufficiently high and if only then the main part of the reactants reacts, especially in the case of slower reactions, it is possible to wait a while for the recording of the first spectrum, provided the reaction rate of the reactants is subsequently sufficiently high to to measure them by measurement, but it will be advantageous if the first Spectrum recorded within one to 1000 milliseconds after the reactants are mixed.
  • differential spectra of two spectra recorded at any time can be formed to identify the active ingredient.
  • the difference spectrum is preferably formed with the spectrum recorded immediately after the reactants have been mixed (measurement time t 0 ).
  • a spectrum that has a large temporal distance from this spectrum is preferably selected as the second spectrum. If more than two reactants are used in the measurement, the reaction is preferably started by adding the reactant which leads to the complex formation to be investigated.
  • Substances are used as reactants whose pharmaceutical or plant protection effects are suspected and which are to be investigated in more detail.
  • Reactants can be, for example, potential drugs, potential herbicides, fungicides or insecticides that are able to form complexes.
  • the active substances in the process according to the invention are preferably substances which have a physiological effect in the plant, animal or human body, such as, for. B. hormones, vitamins, enzymes, phar aka or pesticides.
  • the active ingredients of its reactants such as proteins, for example enzymes such as ECE or ACE, receptors such as glutamate receptors, antibodies, protein inhibitors such as PAI, mediators, for example interferons such as gamma-interferon, interleukins such as interleukin-2 or interleukin-6, transcription factors such as Spl, Regulator proteins, translocators or chaperones are mentioned as examples.
  • Low-molecular substances are understood to mean organic chemical compounds that for example optionally substituted aliphatic or aromatic heterocycles, aromatics, saturated or unsaturated aliphatics, amines, ketones, thioketones, alcohols, thiols, esters, amides, ethers, thioethers, nitriles, isonitriles, aldehydes or their derivatives.
  • Active substances which release a ligand which finally forms a complex as a reactant with the further reactant (s) can also be detected with the method according to the invention.
  • the identification of complex formation between proteins is less preferred since proteins, for example as active ingredients, cannot be administered orally and often lead to allergic reactions.
  • the complex formation between proteins, DNA or RNA and low-molecular substances is preferably investigated.
  • At least one of the reactants in the method according to the invention can be a protein or a DNA; at least one other reactant should be a low molecular weight substance. Interactions between long and short chain DNA or RNA can also be detected.
  • the middle IR range between 2500 and 12500 nm is preferably used.
  • a second IR or FTIR spectrum is then recorded (time t n ).
  • reaction conversion to date is documented in the second IR or FTIR spectrum.
  • This reaction conversion can be represented by forming a difference spectrum from the first spectrum, for example at to and the second spectrum at t n .
  • the difference spectrum consists essentially of a straight line, no reaction has taken place, since in this case the concentration of the reactants does not change. Binding of the reactants is therefore evident in a difference spectrum which has a band structure.
  • Complexes in the process according to the invention are understood to mean all covalent or non-covalently bound reactants or their parts.
  • Examples of non-covalent bonds here are bonds via van der Waals forces, via hydrogen bonding or via ionic bonds. According to the invention, non-covalently bound reactants or their parts are preferred.
  • An important advantage of the process according to the invention is that the process sequence can be automated, so that the reactant complexes can be formed quickly either in succession or in parallel.
  • So-called mass screening processes are particularly important when developing new drugs.
  • a protein is identified that is related to the manifestation of a disease, for example.
  • the task now is to find a suitable drug that inhibits this so-called target protein.
  • the target protein can be obtained in large quantities and with high purity from the corresponding biological material.
  • a variety reagents, the pharmaceutical effectiveness of which is suspected, are tested to determine whether they have the desired inhibitory activity.
  • the number of reagents to be tested is generally very large; it can be 5-, 6- or even 7-digit so that the use of a fast, automatic screening method is of crucial economic importance.
  • the method according to the invention can take on this task.
  • the prerequisites for testing a large number of reagents are created.
  • Another important advantage of the method is that the standard microtiter plates that are usually used can be used without any problems. Since the trend is towards even smaller microtiter plates with 384 or even 864 wells, which have an even smaller volume of approximately 100 ⁇ l or approximately 50 ⁇ l, the small amount of sample required is of particular importance in the method according to the invention and in the device according to the invention Importance. Further important advantages and the basics for the suitability of the method mass screening methods are that no water has to be used and that the device can be used for examinations without design changes for a multitude of tests.
  • Figure 1 shows the embodiment of the device in a first operating state.
  • Fig. 3 shows the embodiment of the device in a third operating state.
  • 1 shows the device in a first operating state, in which the valves 3 and 4 are filled with a test substance or with a target protein.
  • the test substances are placed in a standard microtiter plate 11 on an xyz positioning table and the target protein in a storage container 9.
  • Valves 3 and 4 are rotary valves known from HPLC technology (from Valco); they are switched in the position shown so that they can be filled with the two low-pressure pumps 6 and 7 with a test substance from the standard microtiter plate 11 or with the target protein from the storage container 9. Any excess is directed to the sewage system (not shown) in both cases.
  • the valves 3 and 4 are switched.
  • the test substance and the target protein are mixed using the high-pressure pump 8, which is connected to a storage container 10 for distilled water, and transported into the IR cuvette 2 in the FTIR spectrophotometer 1.
  • valve 5 is switched so that the test substance and the target protein are isolated in a closed line system.
  • the measuring cell is rinsed with distilled water before the cycle is run through again.
  • the device is essentially made up of HPLC components.
  • the high-pressure pump 8 is an HPLC pump (Alltech), which is capable of continuous high-pressure operation. All liquid lines and connections consist of HPLC components that can be loaded up to 400 bar. To protect the HPLC pump, only distilled water is pumped.
  • the selected arrangement of the HPLC rotary valves 3, 4 and 5 brings the additional advantages that are important for mass screening efficient cleaning of the system and reduced sample material consumption.
  • the flow of the distilled water from the reservoir 10 is diverted by the high pressure pump 8 instead of being stopped to stop the flow through the IR cuvette. This protects the pump and results in a faster response time. This also short-circuits the input and output lines of the IR cell, which is why the overpressure is quickly equalized and changes in layer thickness due to bulging of the IR cell are eliminated.
  • Flow rates of up to 40 ml / min can be achieved with the device shown in the figures, which corresponds to an exchange of the contents of the IR cuvette within 15 ms. A pressure of up to approx. 150 bar is recorded. The flow of liquid is diverted with the aid of valve 5 in 20 ms. Each 100 ⁇ l target protein and test substance are sufficient for the acquisition of the FTIR spectra, whereby the optimization of the sample requirement can be reduced by a factor of 3 to 5.

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Medicinal Chemistry (AREA)
  • Microbiology (AREA)
  • Cell Biology (AREA)
  • Food Science & Technology (AREA)
  • Biotechnology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Spectrometry And Color Measurement (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Optical Measuring Cells (AREA)

Abstract

L'objectif de l'invention est de développer un procédé et un dispositif pour l'identification de principes actifs, permettant de détecter la formation de complexes entre des réactifs. Cet objectif est atteint grâce à un procédé selon lequel on mélange au moins deux réactifs se transformant pour former un complexe et on définit, à un premier moment, le spectre infrarouge des différents réactifs qui ne se sont pas encore transformés dans le mélange et on mesure, à un second moment, en effectuant au moins une autre mesure d'infrarouge, le complexe formé par les réactifs, on établit la différence des deux spectres mesurés à des moments différents et on sélectionne comme principe actif les réactifs dont le spectre différentiel présente une structure à bandes. L'invention concerne également un dispositif dans lequel deux tiroirs rotatifs à échantillons sont remplis, au moyen de deux pompes, avec le réactif et le composé organique, les tiroirs rotatifs à échantillons sont mis en communication pour créer un espace fermé, et, au moyen d'une troisième pompe, un mélange est produit dans ledit espace fermé et amené à une cuve à infrarouges.
PCT/EP1998/005328 1997-09-04 1998-08-21 Procede et dispositif d'identification de principes actifs Ceased WO1999012017A1 (fr)

Priority Applications (7)

Application Number Priority Date Filing Date Title
EP98946404A EP1009999B1 (fr) 1997-09-04 1998-08-21 Procede et dispositif d'identification de principes actifs
AT98946404T ATE208896T1 (de) 1997-09-04 1998-08-21 Verfahren und vorrichtung zur identifizierung von wirkstoffen
US09/508,416 US6429015B1 (en) 1997-09-04 1998-08-21 Method for identifying active substances
CA2302791A CA2302791C (fr) 1997-09-04 1998-08-21 Procede et dispositif d'identification de principes actifs
JP2000508971A JP3357350B2 (ja) 1997-09-04 1998-08-21 作用物質を確認する方法および装置
DK98946404T DK1009999T3 (da) 1997-09-04 1998-08-21 Fremgangsmåde ved identificering af aktive stoffer og indretning til udøvelse af fremgangsmåden
DE59802164T DE59802164D1 (de) 1997-09-04 1998-08-21 Verfahren und vorrichtung zur identifizierung von wirkstoffen

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19738566.4 1997-09-04
DE19738566A DE19738566C2 (de) 1997-09-04 1997-09-04 Verfahren und Vorrichtung zur Identifizierung von Wirkstoffen

Publications (1)

Publication Number Publication Date
WO1999012017A1 true WO1999012017A1 (fr) 1999-03-11

Family

ID=7841101

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1998/005328 Ceased WO1999012017A1 (fr) 1997-09-04 1998-08-21 Procede et dispositif d'identification de principes actifs

Country Status (9)

Country Link
US (1) US6429015B1 (fr)
EP (1) EP1009999B1 (fr)
JP (1) JP3357350B2 (fr)
AT (1) ATE208896T1 (fr)
CA (1) CA2302791C (fr)
DE (3) DE19738566C2 (fr)
DK (1) DK1009999T3 (fr)
ES (1) ES2163890T3 (fr)
WO (1) WO1999012017A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1384988A1 (fr) * 2002-07-22 2004-01-28 The Automation Partnership (Cambridge) Limited Système d'analyse infrarouge

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6558916B2 (en) 1996-08-02 2003-05-06 Axiom Biotechnologies, Inc. Cell flow apparatus and method for real-time measurements of patient cellular responses
US5804436A (en) 1996-08-02 1998-09-08 Axiom Biotechnologies, Inc. Apparatus and method for real-time measurement of cellular response
US6280967B1 (en) * 1996-08-02 2001-08-28 Axiom Biotechnologies, Inc. Cell flow apparatus and method for real-time of cellular responses
US6054711A (en) * 1997-11-12 2000-04-25 Millennium Pharmaceuticals, Inc. Methods for identifying biological macromolecule interactions with compounds, particularly in complex mixtures
WO2000039562A1 (fr) * 1998-12-23 2000-07-06 Aventis Animal Nutrition S.A. Analyse de vitamines par spectroscopie proche infrarouge
DE19909692C1 (de) * 1999-03-05 2000-03-16 Karlsruhe Forschzent Durchflußmeßzelle zur Untersuchung einer schnell ablaufenden chemischen Reaktion
US6907351B2 (en) 2001-08-01 2005-06-14 Aventis Animal Nutrition S.A. Customer-based prediction method and system using near infrared reflectance spectra of materials
KR100845682B1 (ko) 2004-03-18 2008-07-11 산요덴키가부시키가이샤 반도체 레이저 소자 및 그 제조 방법
DE102004062166B4 (de) * 2004-12-20 2007-03-22 Anatox Gmbh & Co. Kg Vorrichtung zur Probenentnahme und zum Probentransfer
US20060205082A1 (en) * 2005-03-10 2006-09-14 Middleton John S Reaction rate determination
AU2009289244A1 (en) * 2008-09-05 2010-03-11 Basf Se Method for testing substances or substance mixtures and the use thereof
EP3786618A1 (fr) * 2019-08-26 2021-03-03 Veterinärmedizinische Universität Wien Procédé d'analyse d'un échantillon de dialyse péritonéale

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1985004478A1 (fr) * 1984-03-23 1985-10-10 Sähköliikkeiden Oy Procede de mesure de la teneur en hydrocarbures d'un liquide
US5339255A (en) * 1992-02-14 1994-08-16 Fuji Photo Film Co., Ltd. Method of controlling synthesis reaction
WO1996018096A1 (fr) * 1994-12-09 1996-06-13 United Utilities Plc Detection quantitative d'especes chimiques

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS56155835A (en) * 1980-05-02 1981-12-02 Olympus Optical Co Ltd Component analyzing method
DD231649A1 (de) * 1984-12-17 1986-01-02 Akad Wissenschaften Ddr Einrichtung zur messung von differenzspektren geloester stoffe
US4722830A (en) * 1986-05-05 1988-02-02 General Electric Company Automated multiple stream analysis system
US5519220A (en) * 1994-06-28 1996-05-21 Janos Technology Inc. FTIR chemical reaction monitor
US5677191A (en) * 1995-09-05 1997-10-14 Janos Technology Inc. Organic chemical compound test papers and method of using same
US6054711A (en) * 1997-11-12 2000-04-25 Millennium Pharmaceuticals, Inc. Methods for identifying biological macromolecule interactions with compounds, particularly in complex mixtures

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1985004478A1 (fr) * 1984-03-23 1985-10-10 Sähköliikkeiden Oy Procede de mesure de la teneur en hydrocarbures d'un liquide
US5339255A (en) * 1992-02-14 1994-08-16 Fuji Photo Film Co., Ltd. Method of controlling synthesis reaction
WO1996018096A1 (fr) * 1994-12-09 1996-06-13 United Utilities Plc Detection quantitative d'especes chimiques

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1384988A1 (fr) * 2002-07-22 2004-01-28 The Automation Partnership (Cambridge) Limited Système d'analyse infrarouge

Also Published As

Publication number Publication date
DE59802164D1 (de) 2001-12-20
DE29809591U1 (de) 1998-09-24
US6429015B1 (en) 2002-08-06
JP2001515205A (ja) 2001-09-18
CA2302791C (fr) 2010-07-13
DE19738566C2 (de) 1999-07-29
EP1009999B1 (fr) 2001-11-14
ATE208896T1 (de) 2001-11-15
EP1009999A1 (fr) 2000-06-21
DK1009999T3 (da) 2002-03-25
JP3357350B2 (ja) 2002-12-16
CA2302791A1 (fr) 1999-03-11
ES2163890T3 (es) 2002-02-01
DE19738566A1 (de) 1999-03-18

Similar Documents

Publication Publication Date Title
DE69821475T2 (de) Verwendung von eindimensionaler kernspinresonanz fur identifizierung von liganden fur ziel-biomolekule
DE68909962T2 (de) Verfahren und Vorrichtung zur quantitativen Bestimmung von Trihalomethanen.
EP1009999B1 (fr) Procede et dispositif d'identification de principes actifs
DE2953524C2 (fr)
DE69330834T2 (de) Quantitative detektierung von makromolekülen mit hilfe von fluoreszierenden oligonukleotiden
EP0906572B1 (fr) Masquage de la fluorescence et de la luminescence d'arriere plan lors de l'analyse optique d'essais biomedicaux
DE69125992T2 (de) Verfahren und Kit für Immunoassay
DE69213315T2 (de) Reagenzien und Verfahren zur Zellanalyse im Harn
DE2628158B2 (de) Verfahren zur Fluoreszenzspektroskopie einer Targetsubstanz
DE4124920A1 (de) Biochemischer analysator und in dem analysator verwendete prismazelle fuer abgeschwaechte totalreflektion
DE1798423B2 (de) Analysierungsband fuer eine automatische analysierungseinrichtung
DE4029557C2 (de) Verfahren, Gerät und Trennsäule für eine Flüssigkeitschromatographie
DE2600383C3 (de) Analyseverfahren und -vorrichtung zur Bestimmung wenigstens einer primären und einer sekundären Aminosäure in einem Flüssigkeitsprobenstrom
DE112010000814B4 (de) Immunanalytisches Verfahren und immunanalytisches System mit Verwendung der Massenspektrometertechnologie
DE112014001792T5 (de) Molekulare Matrize und Herstellungsverfahren dafür
DE2741862C2 (fr)
WO2006131225A1 (fr) Procede et dispositif destines a la determination quantitative d'analytes dans des echantillons liquides
DE102004010969B4 (de) Verfahren und Vorrichtung zur Isotopenverhältnisanalyse und Verwendung des Verfahrens
DE69431506T2 (de) Überwachung chemischer Zusatzstoffe
DE2341158C3 (fr)
DE60305149T2 (de) Einrichtung zur positionierung einer platte, mit der proben auf einer untersuchungseinrichtung analysiert werden
DE112004000532T5 (de) Verfahren und Vorrichtung zum Verfolgen von Prozessen unter Verwendung eines einzelnen Detektors
EP1705485B1 (fr) Procédure de disposition de la concentration de glucose par de polarisation de la fluorescence
EP0588139B1 (fr) Procédé analytique pour la recherche de constituants toxiques dans des mélanges
DE3908123A1 (de) Analysegeraet

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): CA JP US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 1998946404

Country of ref document: EP

ENP Entry into the national phase

Ref document number: 2302791

Country of ref document: CA

Ref country code: CA

Ref document number: 2302791

Kind code of ref document: A

Format of ref document f/p: F

WWE Wipo information: entry into national phase

Ref document number: 09508416

Country of ref document: US

WWP Wipo information: published in national office

Ref document number: 1998946404

Country of ref document: EP

WWG Wipo information: grant in national office

Ref document number: 1998946404

Country of ref document: EP